Approach to the Patient with Acid-Base Problems

Maintenance of Normal pH normal pH = 7.40 --> [H+] = 40 neq / L H2O + CO2 <--> H2CO3 <--> H+ + HCO3- dietary breakdown of protein (about 80 meq / d normally) 13,000 to 20,000 mM CO2 produced per day

Henderson - Hasselbach Equation H2O + CO2 <--> H2CO3 <--> H+ + HCO3- is equivalent to: pH = 6.1 + log {[HCO3-] /[H2CO3]} pH = 6.1 + log {[HCO3-] / (.03 x pCO2)} which can be approximated by the formula

Remember this formula !!!!! [H+] = 24 x pCO2 / [HCO3-] Normally, [H+] = 40 neq / L Normally, pCO2 = 40 mm Hg Normally, [HCO3-] = 24 meq / L Remember this formula !!!!! This formula is probably the most important one to remember. It relates all three main variables in a simple and useful way. It also shows us that it is the ratio of pCO2 to HCO3 that is most important in determining [H+], and thereby pH.

[H+] = 24 x pCO2 / [HCO3-] This formula is easy to remember The constant is easy to remember (same as the usual [HCO3] level And…most importantly  This formula is probably the most important one to remember. It relates all three main variables in a simple and useful way. It also shows us that it is the ratio of pCO2 to HCO3 that is most important in determining [H+], and thereby pH.

This formula shows that it is the RATIO of CO2 and [H+] = 24 x pCO2 / [HCO3-] This formula shows that it is the RATIO of CO2 and HCO3 which determines pH pCO2 / [HCO3-] This formula is probably the most important one to remember. It relates all three main variables in a simple and useful way. It also shows us that it is the ratio of pCO2 to HCO3 that is most important in determining [H+], and thereby pH.

[H+] = 24 x pCO2 / [HCO3-] Getting from [H+] to pH (or back) Converting from [H+] to pH can be easy if you are a savant, if you carry a calculator, or if you take advantage of the fact that, over the range of physiologic pH, the relationship between [H+] and pH is almost linear This formula is probably the most important one to remember. It relates all three main variables in a simple and useful way. It also shows us that it is the ratio of pCO2 to HCO3 that is most important in determining [H+], and thereby pH.

[H+] = 24 x pCO2 / [HCO3-] pH actual [H+] estimated[H+] 7.10 79 70 This formula is usable because, in the range of pH values we usually deal with, there is a nearly linear relationship between pH and [H+] pH actual [H+] estimated[H+] 7.10 79 70 7.20 63 60 7.30 50 50 7.50 32 30

Regulation of pH – 3 mechanisms Buffering Respiratory regulation of pCO2 Renal regulation of [H+] and [HCO3-]

Regulation of pH – 3 mechanisms Different Mechanisms Different Speeds

Regulation of pH -- mechanisms Buffering -- OCCURS IMMEDIATELY No semipermeable membranes to cross No enzyme activation necessary Everything needed is right at hand

Regulation of pH -- mechanisms Buffering -- OCCURS IMMEDIATELY Respiratory changes OCCUR OVER HOURS Brainstem response to pH Delay in CSF pH changes

Regulation of pH -- mechanisms Buffering -- OCCURS IMMEDIATELY Respiratory changes are INTERMEDIATE Renal changes OCCUR MORE SLOWLY Physiologic changes in renal H+ excretion

Buffering Extracellular almost entirely through bicarbonate it’s concentration is highest small contribution from phosphate H2O + CO2 <--> H2CO3 <--> H+ + HCO3- Intracellular

Buffering Extracellular Intracellular hemoglobin can directly buffer protons H+ entry into RBC matched by exit of Na+ and K+ relationship between pH and measured [K+] hemoglobin can directly buffer dissolved CO2 intracellular conversion of CO2 (and H2O) to H+ and HCO3- -> generation of HCO3- H+ buffered by Hb; HCO3- exchanges for Cl-

Respiratory regulation of pCO2 pCO2 is inversely proportional to VENTILATION Ventilation increases in response to a drop in pH, and falls when pH rises respiratory center in medulla responds to pH “intermediate” between that of CSF and plasma response is rapid (though not instantaneous) response is more predictable for falls in pH than for increases

Renal Regulation of [H+] and [HCO3-] TWO MAJOR FUNCTIONS OF THE KIDNEY (regarding acid-base reg.)

Renal Regulation of [H+] and [HCO3-] TWO MAJOR FUNCTIONS OF THE KIDNEY Reclamation of filtered bicarbonate Excretion of Acid

Renal Regulation of [H+] and [HCO3-] TWO MAJOR FUNCTIONS OF THE KIDNEY Reclamation of filtered bicarbonate a normal occurrence 4000 meq / day in normal persons by far the greatest use of secreted acid Excretion of Acid

Renal Regulation of [H+] and [HCO3-] TWO MAJOR FUNCTIONS OF THE KIDNEY Reclamation of filtered bicarbonate Excretion of Acid titratable acidity ammonium formation free H+ excretion

Renal Regulation of [H+] and [HCO3-] Factors which effect renal acid excretion (bicarbonate reclamation) ACID EXCRETION IS STIMULATED BY: Acidemia Hypercapnea Volume depletion (?mediated by angiotensin II) Chloride depletion ?? Hypokalemia Aldosterone

Renal Regulation of [H+] and [HCO3-] Factors which effect renal acid excretion (bicarbonate reclamation) ACID EXCRETION IS INHIBITED BY: Alkalemia Elevated [HCO3-] Hypocapnea ? Hyperkalemia

Renal Regulation of [H+] and [HCO3-] Remember: Compared to BUFFERING and RESPIRATORY adaptation, RENAL compensatory mechanisms take a bit longer.

Definitions Acidemia = pH below the normal of ~ 7.40 Alkalemia = pH above the normal of ~ 7.40 Metabolic acidosis = loss of [HCO3-] or addition of [H+] Metabolic alkalosis = loss of [H+] or addition of [HCO3-] Respiratory acidosis = increase in pCO2 Respiratory alkalosis = decrease in pCO2

The ANION GAP Na+ - Cl- - HCO3- = 8-12 normally mainly proteins, phosphates, and sulfates

The ANION GAP Na+ - Cl- - HCO3- = 8-12 normally mainly proteins, phosphates, and sulfates In any patient with an acid-base disturbance, and especially in those with a metabolic acidosis, you should calculate the Anion Gap

The ANION GAP Na+ - Cl- - HCO3- = 8-12 normally mainly proteins, phosphates, and sulfates In any patient with an acid-base disturbance, and especially in those with a metabolic acidosis, you should calculate the Anion Gap BRAINSTEM REFLEX

High Anion Gap Metabolic Acidosis USUALLY FROM ADDITION OF ACID Ketoacidosis DKA, Alcoholic KA, Starvation Lactic acidosis hypoperfusion; other causes Ingestions ASA, Ethylene glycol, methanol Renal insufficiency inability to excrete acid

Normal Anion Gap Metabolic Acidosis Rise in Chloride matches the decrease in HCO3

Normal Anion Gap Metabolic Acidosis Renal Disease proximal or distal RTA renal insufficiency (HCO3- loss) hypoaldosteronism / K+ sparing diuretics Loss of alkalai diarrhea ureterosigmoidostomy Ingestions carbonic anhydrase inhibitors

Compensation A “simple” acid-base disturbance is one with a primary problem (respiratory or metabolic, acidosis or alkalosis) leading to a compensation in the other arm.

Compensation A “simple” acid-base disturbance is one with a primary problem (respiratory or metabolic, acidosis or alkalosis) leading to a compensation in the other arm. Primary metabolic problem – respiratory compensation Primary respiratory problem – metabolic compensation

Compensation THREE THINGS TO REMEMBER Compensation is not immediate Compensation is not complete The pCO2 and HCO3 move in the same direction

Compensation - Rules These formulas are EMPIRICALLY DERIVED from observation and measurement.

Compensation - Rules Respiratory Compensation for Metabolic Changes Metabolic acidosis pCO2 decreases by 1.2 x the drop in [HCO3-] Metabolic alkalosis pCO2 increases by .7 x the rise in [HCO3-] less predictable than the comp. for acidosis COMPENSATION IS USUALLY NOT COMPLETE important !!

Compensation - Rules Metabolic Compensation for Respiratory Changes Respiratory Acidosis ACUTE: [HCO3-] increases by .1 x the rise in pCO2 CHRONIC: [HCO3-] increases by .35 x the rise in pCO2 Respiratory Alkalosis ACUTE: [HCO3-] decreases by .2 x the fall in pCO2 CHRONIC : [HCO3-] decreases by .5 x the fall in pCO2 COMPENSATION IS USUALLY NOT COMPLETE

Approach to the Patient History and Physical Examination In the majority of cases you should be able to predict, qualitatively, the type of disturbance Examples: a patient with septic shock (hypoperfusion) a patient with severe COPD a patient with one day of worsening asthma 1) We would expect to see a lactic acidosis (high anion gap metabollic acidosis), probably with some degree of respiratory compensation. 2) We would expect a chronic respiratory acidosis with a metabolic compensation. 3) We would expect an acute respiratory alkalosis with some metabolic compensation. The degree of respiratory alkalosis would depend on the length and severity of the attack. The degree of compensation would depend on the length and severity of the respiratory alkalosis.

Approach to the Patient Is the patient ACIDEMIC or ALKALEMIC ? What is the [HCO3-] ? elevated ---- metabolic alkalosis decreased -- metabolic acidosis What is the Anion Gap What is the pCO2 ? elevated --- respiratory acidosis decreased -- respiratory alkalosis Is the degree of compensation what you expect?

Notation for Laboratory Values Na+ Cl- BUN Glu K+ HCO3- Cr. pH pCO2 pO2 base excess FIO2 ON